Human induced pluripotent stem cells have pluripotency to be differentiated into triploblastic (endoderm, mesoderm, and ectoderm) cells constituting the human body and the characteristic of self-renewal capable of continuously undergoing cell divisions. Therefore, various studies have been performed on their differentiation into cells necessary for regenerative medicine, e.g., nerve cells, liver cells, blood cells, etc. In order to obtain differentiated cells from human induced pluripotent stem cells, a Fluorescent Activated Cells Sorter (FACS) or a Magnetic Cell Sorting (MACS) may be used. The FACS method includes inducing differentiation of human induced pluripotent stem cells into specific cells and separating the cells marked by antibodies of specific surface markers of the differentiated cells through FACS to obtain only the differentiated cells (Fukuda, H et al., “Fluorescence-Activated Cell Sorting-Based Purification of Embryonic Stem Cell-Derived Neural Precursors Averts Tumor Formation After Transplantation” Stem Cells (2006)(24.3: 763-771)). In the MACS method, the differentiated cells are obtained using antibody markers and magnetism (David, R et al., “Magnetic Cell Sorting Purification of Differentiated Embryonic Stem Cells Stably Expressing Truncated Human Cd4 as Surface Marker” Stem Cells (2005) (23.4: 77-82)). The MACS method has an advantage in that it can get rid of the danger of exposing cells to laser being applied during the separation using the FACS.
However, both FACS and MACS methods cannot exclude the possibility of the mixed presence of undifferentiated induced pluripotent stem cells, and thus there is a technical limitation in separating only the differentiated cells with 100% purity. In particular, it is possible that undifferentiated cells may be mixed in the differentiated cells derived from induced pluripotent stem cells. Accordingly, in the development of a cell therapeutic agent using induced pluripotent stem cells, there is a continuing controversy regarding the danger of formation of teratoma, a tumor derived from undifferentiated pluripotent stem cells. Therefore, there is a demand in the art on the development of a technology capable of selectively removing undifferentiated cells having the potential danger of teratoma, without affecting the differentiated cells.
Numerous journal articles and patent documents are referred to herein over the entire specification and indicated as referred to. The disclosure of the cited journal articles and the patent documents are incorporated herein in their entirety by reference to further elucidate the level of the technologies to which the present invention belongs and the details of the present invention.